tbuckley/cabot-search huggingface dataset:
Breast cancer in young women in Guatemala: A retrospective comparative cohort study.
Authors: Alba Kihn-Alarcón, Vicky de Falla, Mauricio Siliézar, Loida Isabel Orozco, Carlos García, Javier Figueroa, Edgar Ruiz, María Fernanda Toledo-Ponce, Mariluna García-Rivera, Sonia Dávila, Liliana Sobrevilla, Lauren E Henke, Hiram Alberto Gay, Jacaranda Van Rheenen, Angel Velarde
Journal: Journal of Clinical Oncology (2022)

e13523 Background: In Guatemala, breast cancer is the most common malignancy among women, the socioeconomic variability among the population directly affects the access to screening and treatment, and little is known about the behavior of the disease among younger women, reason why the aim of our study is to describe the clinico-pathological characteristics in this population. Methods: Retrospective study performed of patients with a confirmed biopsy of breast cancer that were treated at Liga Nacional Contra el Cáncer - INCAN in Guatemala, the largest cancer center in the country. From medical records, we obtained: clinico-pathological and treatment (surgery, radiotherapy, endocrine therapy) data and compared results between ≤40 years and &gt;40 years old women. Results: The study identified 1,347 patients, 190 (16.42%) ≤40 years old women and 1,157 (83.57%) &gt;40 years old. The mean age at diagnosis among patients was 36 vs. 56 years old, respectively (p&lt;0.01). According to our findings, even though most patients came from the region I of the country that is the capital city, there was a higher percentage of patients from the West regions (VI, VII) that belonged to the younger group 22.22% vs 10.58%. Furthermore, 74.4% of ≤40 years old patients were staged as locally advanced or metastatic vs &gt;40 year old patients (48.04%), and 65.34% of ≤40 years old were found to have triple negative and Her2 enriched subtypes vs 46.13% in &gt;40 years old (p&lt;0.01). Conclusions: Young breast cancer patients in Guatemala are characterized by being diagnosed at locally advanced and advanced stages of the disease with more biologically aggressive subtypes such as triple negative and her2 enriched. [Table: see text]
Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses
Authors: Takamichi Kuwahara, Kazuo Hara, Nobumasa Mizuno, Shin Haba, Nozomi Okuno, Yasuhiro Kuraishi, Daiki Fumihara, Takafumi Yanaidani, Sho Ishikawa, Tsukasa Yasuda, Masanori Yamada, Sachiyo Onishi, Keisaku Yamada, Tsutomu Tanaka, Masahiro Tajika, Yasumasa Niwa, Rui Yamaguchi, Yasuhiro Shimizu
Journal: Endoscopy (2022)

Abstract Background There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). Methods Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. Results 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84–0.97), 0.94 (0.88–0.98), 0.82 (0.68–0.92), and 0.91 (0.85–0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90–0.99), PASC 1.00 (0.05–1.00), ACC 1.00 (0.22–1.00), MPT 0.33 (0.01–0.91), NEC 1.00 (0.22–1.00), NET 0.93 (0.66–1.00), SPN 1.00 (0.22–1.00), chronic pancreatitis 0.78 (0.52–0.94), and AIP 0.73 (0.39–0.94). Conclusions Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.
Dietary intervention preserves β cell function in mice through CTCF-mediated transcriptional reprogramming
Authors: Ruo-Ran Wang, Xinyuan Qiu, Ran Pan, Hongxing Fu, Ziyin Zhang, Qintao Wang, Haide Chen, Qing-Qian Wu, Xiaowen Pan, Yanping Zhou, Pengfei Shan, Shusen Wang, Guoji Guo, Min Zheng, Lingyun Zhu, Zhuo-Xian Meng
Journal: The Journal of Experimental Medicine (2022)

Pancreatic β cell plasticity is the primary determinant of disease progression and remission of type 2 diabetes (T2D). However, the dynamic nature of β cell adaptation remains elusive. Here, we establish a mouse model exhibiting the compensation-to-decompensation adaptation of β cell function in response to increasing duration of high-fat diet (HFD) feeding. Comprehensive islet functional and transcriptome analyses reveal a dynamic orchestration of transcriptional networks featuring temporal alteration of chromatin remodeling. Interestingly, prediabetic dietary intervention completely rescues β cell dysfunction, accompanied by a remarkable reversal of HFD-induced reprogramming of islet chromatin accessibility and transcriptome. Mechanistically, ATAC-based motif analysis identifies CTCF as the top candidate driving dietary intervention-induced preservation of β cell function. CTCF expression is markedly decreased in β cells from obese and diabetic mice and humans. Both dietary intervention and AAV-mediated restoration of CTCF expression ameliorate β cell dysfunction ex vivo and in vivo, through transducing the lipid toxicity and inflammatory signals to transcriptional reprogramming of genes critical for β cell glucose metabolism and stress response.
Effect of obesity on resection margins in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemotherapy.
Authors: Palash Asawa, Urwat Til Vusqa, Rahul Karna, Shivani Shah, Ryan Sweeney, Thejus Jayakrishnan, Srividya Srinivasamaharaj, Yazan Samhouri, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2022)

e16229 Background: Obesity has been associated with decreased survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, exact reasons remain unclear. Reduced response to chemotherapy because of obesity-induced desmoplasia has been proposed as a mechanism for the suboptimal response to treatment and therefore worse outcome. To this end, we attempted to determine the effect of obesity on the efficacy of neoadjuvant chemotherapy in patients with resectable and potentially resectable PDAC who underwent surgical resection. We assessed rates of microscopic tumor-free margins as a surrogate for treatment response. Methods: We performed a retrospective review of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Obesity was defined as BMI &gt; 30 kg/m 2 . Patients with resectable and potentially resectable disease who eventually received surgical treatment were included. Demographics, treatment details, and surgical pathology results were reviewed. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables, respectively. A p value of &lt; 0.05 was considered as level of significance. Results: Out of 121 patients who received and completed treatment at our institution, 29 patients underwent neoadjuvant chemotherapy followed by surgical resection. Most patients were female (61%), Caucasians (90%), had stage I (76%) and potentially resectable disease (72%). Eleven (38%) patients were categorized as obese and remaining non-obese. Among patients who underwent surgery after neoadjuvant chemotherapy, 10 out of 11 patients (90.9%) had microscopic tumor-free margins in the obese group when compared to 17 out of 18 patients (94.4%) in the non-obese group. (Table). Conclusions: Our study revealed no significant difference in obese patients compared to non-obese patients in terms of tumor-free margins assessed microscopically after surgical resection. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity on treatment outcomes in resectable and potentially resectable pancreatic cancer patients treated with neoadjuvant chemotherapy.[Table: see text]
The impact of COVID-19 lockdown measures on rates of febrile neutropenia in a cohort of Irish patients receiving chemotherapy.
Authors: David Synnott, James Cook, Deirdre O'Mahony, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2022)

e18784 Background: Febrile neutropenia in patients receiving chemotherapy is a life-threatening condition requiring prompt attention. This condition may also result in dose reductions, delays, or discontinuations of chemotherapy which compromise patient outcomes. This study seeks to evaluate the impact of COVID19 “lockdown” public health measures in Ireland on the incidence of febrile neutropenia in patients who were receiving cytotoxic chemotherapy regimens. Methods: All patients receiving chemotherapy at the Bon Secours Hospital Cork who were admitted with neutropenia and fever during two separate time periods were included in the study: 1 st April 2018 to 31 st March 2019 (“pre-pandemic year”) and 1 st April 2020 to 31 st March 2021 (“pandemic year”). The pandemic year selected equates to a period of heightened infection control measures in Irish society, featuring public health advice re social distancing, routine mask wearing in public and successive lockdown waves. Retrospective chart review was performed on all patients admitted to the oncology inpatient ward who had blood cultures on admission to determine the number of these patients who were neutropenic at the time of blood culture draw. Similarly, pharmacy records were accessed to determine the number of unique chemotherapy items dispensed in each year in order to establish a rate of febrile neutropenia episodes per 100 chemotherapy items dispensed for each period. The incident rate ratio was calculated using the Exact Poisson Test. Results: During the pre-pandemic year there were 57 individual admissions with febrile neutropenia compared with 32 admissions during the pandemic year. There were 4581 chemotherapy units dispensed during the pre-pandemic year compared to 4628 during the pandemic year. The rate of febrile neutropenia episodes per 100 chemotherapy units dispensed was 1.24 (95% CI 0.94, 1.61) in the pre-pandemic year and 0.69 (95% CI 0.47, 0.98) in the pandemic year. The incident rate ratio is 1.80 (95% CI 1.14, 2.87, two-sided P = 0.007). 9 of 57 (16%) admissions in the pre-pandemic year were associated with positive blood cultures compared with 4 of 32 (13%) in the pandemic year (not significant by Fisher's exact test). Conclusions: Increased precautionary infection control measures during the COVID19 pandemic public health restrictions correlated with a significant reduction in the rate of febrile neutropenia amongst patients receiving cytotoxic chemotherapy. This suggests that there may be a role for similar measures for this patient cohort in the post-pandemic period. Options which patients may consider to employ include social distancing, wearing face-coverings and restricting social contacts while at risk of neutropenia from cytotoxic chemotherapy regimens.
Long-term outcomes of a randomized controlled clinical trial comparing the efficacy of cabazitaxel versus docetaxel as second-line or above therapy in recurrent head and neck cancer.
Authors: Kavita Prakash Nawale, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Sachin Babanrao Dhumal, Atanu Bhattacharjee, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

e18008 Background: Long term outcomes (&gt; 2 years or above) are rarely reported in studies with second line or beyond systemic therapies in head and neck squmouas cell carcinoma (HNSCC). Methods: Recurrent or relapsed adult HNSCC, with ECOG PS 0-2 who have been exposed to at least one line of chemotherapy were 1:1 randomized between Docetaxel (75 mg/m2) and Cabazitaxel (20 mg/m2). The chemotherapy was given till progression or development of intolerable side effects. The outcomes reported are long term overall survival(OS) and progression free survival (PFS) and factors impacting overall survival. Results: On the intention to treat analysis (n = 92), at the time of data censoring, 92 patients had died. The median overall survival was 112 days (95% CI 81 to 178 days) in the cabazitaxel arm versus 192 days (95% CI 153 to 259 days) in the Docetaxel arm (P = 0.048). In cabazitaxel arm, the one year OS was 6.5% (95% CI 1.6-16.06), 2 year OS was 2.17% (95% CI 0.17-9.95) and 3 years was 2.17% (95% CI 0.17-9.95). While the corresponding figures in the docetaxel arm were 21.7% (95% CI 11.23-34.46), 0% and 0%. The median progression-free survival was 21.0 days (95% CI 16.0-42.0 days) in the Cabazitaxel arm versus 57.5 days (95% CI 26.0-85.0 days) in the Docetaxel arm (P = 0.02). Among the tested factors age (p = 0.037) and site of primary(p = 0.023) had an impact on OS. Conclusions: In this phase 2 randomised study, cabazitaxel has inferior PFS and OS than docetaxel. Hence docetaxel remains the option of choice when cytotoxic chemotherapy needs to be used as second line or beyond setting in HNSCC. Clinical trial information: CTRI/2015/06/005848.
Primary language, race, and location of care as main determining factors of decision to opt out of personalized breast cancer risk assessment.
Authors: Angela Rutkowski, Shirlene Paul, Jordan Lieberenz, Lisa Stempel, Mia Alyce Levy, Rosalinda Alvarado
Journal: Journal of Clinical Oncology (2022)

e18567 Background: Personalized breast cancer risk assessment (CRA) and genetic counseling/testing for women have been shown to improve interventional and clinical outcomes. However, despite CRA being routinely offered to all women at our institution, not all women choose to opt into the program. This study evaluated the demographic distribution of patients that opted out of the CRA to identify potential components influencing this substantial decision. Methods: Our medical center, located in four urban and suburban locations, piloted a clinical framework to provide CRA to all women between the ages of 25 and 75 with a qualifying mammogram. In this single institution retrospective study, we analyzed differences among patients who opted out of the program between July 20, 2020 and July 19, 2021. Data elements extracted from the electronic medical record include race, primary language, location of care, and decision to partake in CRA. Overall Chi-square tests and all pairwise comparisons with Bonferroni correction were used to statistically determine the impact of various demographics on opting out. Results: 18726 women met criteria for inclusion and 2717 (14.5%) declined CRA. Within their respective racial groups, 122 (17.6%) Asian, 1175 (16.3%) Black, 455 (14.2%) Hispanic, 112 (15%) Other, and 853 (12.4%) White opted out. Within their identified primary language, 2370 (13.7%) English, 231 (23.1%) Spanish, 35 (19.7%) Bilingual, and 81 (35.2%) Other opted out. Based on their setting of care, 837 (16.8%) Location A, 1436 (14.2%) Location B, 270 (13.8%) Location C, and 174 (10.6%) Location D opted out. The differences between demographics and opting out were statistically significant for all analyses (p &lt; .0001). Results shown in Table below. Conclusions: The main variables mediating the decision to opt out of CRA are a non-English primary language, non-White race, and location of care, potentially due to inadequate interpretation services, barriers to education, and staffing shortages. Thus, these women are less likely to receive genetic counseling/testing or supplemental screening. Our study is the first to investigate the factors contributing to the uptake of risk assessment. Further study is needed to determine the clinical impact of this striking disparity.[Table: see text]
Preferences for adjuvant immunotherapy in patients with resected stage III melanoma: A discrete choice experiment.
Authors: Ann Livingstone, Alexander M. Menzies, Kirsten Howard, Martin R. Stockler, Rachael L. Morton
Journal: Journal of Clinical Oncology (2022)

9558 Background: Adjuvant immunotherapy has revolutionized the management of resectable melanoma, substantially reducing the risk of recurrence but at the risk of immune-related adverse events (AE). This study aimed to quantify patients' preferences for adjuvant immunotherapy, the influence of varying levels of key attributes, and baseline characteristics associated with preferences. Methods: We performed a discrete choice experiment (DCE), including patients with resected stage III melanoma considering or having received adjuvant immunotherapy. Patients chose between twelve randomly presented choice tasks of two alternative options (adjuvant immunotherapy versus observation without adjuvant immunotherapy). The two options varied across two-three levels of six attributes: chance of 3-year melanoma recurrence, mild, permanent, or fatal AE, drug regimen, and out-of-pocket costs. We calculated the marginal rate of substitution (MRS, how much an individual was willing to trade one attribute for preferred levels of another) and willingness-to-pay (WTP, maximum price to trade their preferred attributes) per year. Results: One hundred and sixteen patients completed the DCE. Patients chose adjuvant immunotherapy over observation without adjuvant immunotherapy in 70% of choice tasks. Patients preferred adjuvant immunotherapy with reduced probabilities of recurrence (OR 0.76, 95% CI 0.70-0.83, p&lt;0.001), fatal AE (OR 0.60, 95% CI 0.44-0.80, p=0.006), permanent AE (OR 0.94, 95% CI 0.89-0.99, p=0.046), and lowered out-of-pocket costs, for those with lower incomes (OR 0.63, 95% CI 0.47-0.85, p=0.003) and higher incomes (OR 0.84, 95% CI 0.15-4.86, p=0.064). Patients accepted an increase in their chance of mild AE from 1% to 37% (OR 2.06, 95% CI 1.13-3.78, p=0.019) in return for adjuvant immunotherapy. Willingness-to-pay was lower for patients with incomes that were lower rather than higher: US$595 (95% CI US-$555 to 1,305) and US$1,638 (95% CI US$ -1,235 to 3,419) per year for adjuvant immunotherapy with an absolute reduction of 1% in the 3-year risk of recurrence. Conclusions: Almost three-quarters of patients preferred adjuvant immunotherapy over observation without adjuvant immunotherapy. Patients were more likely to select immunotherapy if the risk of melanoma recurrence and the chance of fatal AE were reduced. Understanding patient preferences and acceptable trade-offs for adjuvant immunotherapy may allow better-informed decisions for individuals and assist policymakers in decisions about access and subsidization of effective and expensive treatments.
Endocervical adenocarcinoma biomarkers for immunotherapy: Descriptive analysis.
Authors: Victoria Cerda, Nooshin Karamzadeh, Marla Scott, Nolan Kinne, Christopher Mayer, Kristin Taylor, Andrew John Li, Kenneth H. Kim, Fabiola Medeiros, Bonnie Balzer, Bj Rimel
Journal: Journal of Clinical Oncology (2022)

e17526 Background: Adenocarcinoma and adenosquamous carcinoma of the cervix are subtypes of HPV related cervical cancer. As virally mediated tumors, they have become an obvious choice for immunotherapy treatment approach. Currently, there is little information about the presence of immunological tumor markers among patients with endocervical adenocarcinomas. We hypothesized cervical adenocarcinomas highly express immunotherapy markers. Here we characterize the protein status of immunotherapy markers in a large single institution dataset. Methods: An IRB approved retrospective review of cervical adenocarcinoma and adenosquamous carcinoma was performed. We gathered original slides for each patient and performed immunohistochemistry (IHC) for tumor markers CD8, PDL1, TIM3 and LAG3. Demographic and pathologic data was captured. Patients were categorized by positivity percentage for each marker. Descriptive statistics and univariate analysis were used. Results: A total of 97 patients met criteria for the study and slides were available for staining in 68 patients. Demographic data showed a median age of 42 years old with majority of patients identifying as White at 66%, followed by Hispanic (13%), Asian (10%), other (7%) and Black (1%). Of the entire cohort, 75% were adenocarcinoma, 25% were adenosquamous carcinoma. Among those with recorded status, 82% were HPV positive, 14% had metastasis, and 13% had recurrence. On univariate analysis, adenocarcinoma was significantly more common in patients who were LAG3 &lt; 1% or PDL &lt; 1% (p = 0.002, p = 0.007). Patients who were LAG3 &lt; 1% or PDL &lt; 1% were also less likely to have Grade 1 tumors (p = 0.006, 0.03). When analyzing by respective immune marker percentage group there were no statistically significant differences in LVSI, depth of invasion, stage, or recurrence rate. By IHC, 68% were PDL1 &gt; 1% positive, 63% were LAG3 &gt; 1% positive, 100% were TIM3 &gt; 1% positive, 100% were CD8 &gt; 1% positive. Seven of the 68 patients had a recurrence. Of those patients with recurrence, one was treated with immunotherapy. Conclusions: A large proportion of cervical adenocarcinomas displayed immunotherapy targets by IHC suggesting that combined immunotherapy agents may be useful in this population. Further study is needed to assess whether IHC is predictive of outcome or response.[Table: see text]